<scp>EZH2</scp>‐mediated downregulation of <scp>miR</scp>‐155‐5p contributes to prostate cancer cell malignancy through <scp>SMAD2</scp> and <scp>TAB2</scp>

miR-155 exhibits variable expression in different tumors and fulfills diverse biological roles. However, specific molecular mechanisms by which miR-155-5p, which is under-expressed in prostate cancer (PCa), operates are yet to be elucidated. The role of the enhancer of zeste 2 (EZH2)/miR-155-5p axis in PCa was determined by using bioinformatics tools and performing luciferase reporter assay, chromatin immunoprecipitation PCR, CCK-8 assays, cell migration and invasion assays, RNA isolation, reverse transcription quantity (RT-qPCR) and Western blot. miR-155-5p expression would be reduced and promoter methylation would increase in PCa. After 5-Aza-CdR treatment and the integration of the upstream promoter of miR-155-5p into a pGL3-basic/luciferase construct, fluorescence reporter analysis showed that promoter hypermethylation mediated the suppression of miR-155-5p in PCa. Furthermore, EZH2 attached to the miR-155-5p promoter and modulated its expression. EZH2 facilitated the suppression of miR-155-5p through enhanced H3K27me3 methylation, considerably affecting its expression. Through dual-luciferase assays, SMAD2 and TAB2 were confirmed as downstream targets of miR-155-5p, regulating the PCa cellular phenotype governed by miR-155-5p. Lastly, 5-Aza-CdR regulated miR-155-5p expression by modulating its promoter methylation and influenced the malignant behavior of PCa cells. EZH2 promotes H3K27me3 methylation, repressing miR-155-5p expression, which subsequently upregulates the downstream targets SMAD2 and TAB2 and promotes PCa cell proliferation, epithelial-mesenchymal transition (EMT), migration and invasion.